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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many tumor cells are inherently resistant to curative treatment due to an altered pattern of gene expression. It is an attractive and logical proposition to use this difference within the lymphoma cell to eradicate the malignant process. One such new therapeutic approach based on the "silencing" of genes involved in the prevention of apoptosis is Bcl-2 antisense oligonucleotide (AO) therapy. In the field of lymphoma, obvious targets included follicular lymphoma with the t(15;18) translocation, which results in deregulated expression of the Bcl-2 gene, chemoresistance, and subsequent protection against lymphoma cell death. Targeting the initiating codon of the Bcl-2 gene decreases both cell viability and Bcl-2 protein expression in lymphoma and leukemia cell lines that overexpress Bcl-2. Preclinical toxicity studies using a Bcl-2 AO G3139 (Genta, San Diego, CA) show good tolerance at a dose of 10 mg/kg, which is considerably higher than the dose required for good antilymphoma efficacy. In a phase I clinical study, G3139 was well tolerated with minimal toxicity in a dose escalation up to 147.2 mg/m2/d. Evidence of efficacy includes a responder with stage IVB follicular lymphoma who achieved complete clinical and radiologic response that has lasted more than 2 years. The main dose-limiting toxicity has been reversible thrombocytopenia related to the thioate backbone. Other antisense reagents are also in development to combat non-Hodgkin's lymphoma (NHL). These include oligonucleotides that target the messages of the Bcl-X(L) and protein kinase-Calpha (PKCalpha) genes. AOs may also have an application in tumors expressing mutant p53. AOs against MDM2 genes have shown the ability to restore wild-type p53 expression, suggesting that as oncogenic pathways are unraveled, normal cell growth and death patterns may be restored by molecular manipulation. Downregulation of antiapoptosis by AOs in the human setting has low toxicity and antilymphoma activity in cases in which conventional chemotherapy has failed. In the future, antisense therapy followed by chemotherapy may overcome chemoresistance to provide effective therapy for a range of malignancies.
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PMID:Antisense therapy of hematologic malignancies. 1053 Jul 11

Research in chronic lymphocytic leukemia (CLL) has undergone a resurgence of interest in the last decade. While it is obvious that most patients with CLL have typical mature B cells, a number of variants such as splenic lymphoma villous lymphocytes, mantle cell leukemia, and prolymphocytic leukemia need to be considered in the differential diagnosis. This can be established by immunophenotype studies and morphology. Cytogenetic abnormalities are emerging as being of interest, with abnormalities in chromosomes 11 and 17 having major prognostic significance. Immune disregulation is complicated in that along with hypergammaglobulinemia and T-cell dysfunction, the emergence of antibodies directed against hematopoietic cells causes autoimmune hemolytic anemia, neutropenia, and thrombocytopenia. A number of prognostic factors are emerging as being more influential in prognosis and stage, such as serum beta2-microglobulin and soluble CD23. Apoptosis dysregulation is a major feature of CLL, and while no clear pattern has emerged, abnormal levels of bcl2 are common in CLL and bcl2 to bax ratios are also commonly disturbed. Bcl1 levels are commonly increased. Treatment has changed radically. The purine analogs have been demonstrated to be the most active group of drugs in CLL. Combinations of purine analogs, such a fludarabine or 2-chlorodeoxyadenosine, with alkylating agents are emerging as new treatments. The most recent development has been the emergence of two monoclonal antibodies, rituximab (Rituxan; IDEC Pharmaceuticals, San Diego, CA, and Genentech, Inc, San Francisco, CA; directed against CD20) and Campath-1H (directed against CD52 in CLL). The activity of rituximab in lymphoma has been less prominent in small lymphocytic lymphoma (the lymphomatous counterpart of CLL) and this has led to dose escalation studies in CLL with a good level of response. Campath-1H is emerging as another major antibody with marked effect against disease, particularly in the blood and bone marrow. Autologous, allogeneic, and mini-transplant are also being explored extensively. The prognosis for patients with CLL is changing as these new treatments become available.
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PMID:Chronic lymphocytic leukemia. 1056 Oct 25

The purpose of our research was to evaluate the attitude to face the life cycle and the impact that the experience of childhood leukemia may have had in a group of adolescents who had the disease cured. A questionnaire was administered at the Pediatric Hematology Center, San Gerardo Hospital, Monza, Italy, to all former patients age 12 to 20 years and off therapy from leukemia for at least 2 years (total of 116 adolescents) during 1997; 70 patients responded to the mailing and a comparison group of 70 secondary-school students was investigated. The two groups were matched as closely as possible on key characteristics (age, gender, socio-economic level of families, education and occupation of the parents, and geographic area of residence). The Offer Self-Image Questionnaire was the instrument used in this study. Overall, the teenagers in whom leukemia was cured showed a more positive and mature self-image (psychologic, social, attitude toward family, and coping) compared with the student group (statistical evidence, P < 0.05). An effective psychosocial support for patients and their families during their treatment, in addition to medical therapy, is strongly recommended. The majority of survivors of childhood cancer grow successfully without serious psychologic sequelae.
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PMID:Self-image of adolescent survivors of long-term childhood leukemia. 1103 52

The scientific debate on risk relationships between proximity to electric and magnetic fields and the development of childhood leukemia has recently focused on the role of other factors that may be strongly correlated with power lines. Proximity to high traffic density, as defined by major roadways or automobile counts, and associated socioeconomic neighborhood characteristics have been suggested as potentially important confounders. For traffic or socioeconomic status (SES) to confound any EMF effect these factors would need to have their own independent impact on leukemia risk. This study was designed to use geographic information system (GIS) technology to empirically examine the relationship between traffic density and socioeconomic indicators to early childhood leukemia in an urban area of California. Ninety cases of childhood leukemia diagnosed under the age of five between 1988 and 1994 among children born in San Diego County were matched by gender and birth date to a total of 349 children also born in the county and not known to have developed any cancer. Case-control differences were assessed via conditional logistic regression. No significant differences were observed for the neighborhood median family income of the birth residences. When comparing neighborhoods with median annual income > or = $56,000 to those with incomes < or = $18,000 the odds ratio was 0.86 (95% confidence interval 0.31, 2.38). Traffic density was measured using a variety of methods, including information on average daily traffic counts and road characteristics. None of the measures of traffic were associated with case status. Neither SES or traffic density near the birth address as assessed with GIS methods are strong enough risk factors for leukemia to be confounders which could totally explain the effect of another variable (such as wire code). Associations with the diagnosis address or with more direct exposure measures may differ from those reported here.
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PMID:A case-control pilot study of traffic exposures and early childhood leukemia using a geographic information system. 1117 Jan 18

Idiopathic thrombocytopenic purpura is a disorder in which autoantibodies are made to platelets, resulting in accelerated platelet destruction. The diagnosis may be made in outpatients who are previously well or in patients with multiple medical conditions and medications. There are no unequivocal ways to distinguish immune thrombocytopenias from other thrombocytopenias, even with state-of-the-art tests including anti-platelet antibodies, thrombopoietin, glycocalicin, and platelet reticulocyte counts. Clinical evaluation includes ruling out a systemic process such as a viral infection or leukemia. Treatment of idiopathic thrombocytopenic purpura should be individualized. Substantial platelet increases are seen in more than 50% of patients who receive intravenous IgG, intravenous anti-D, steroids, or splenectomy. Two additional agents showing promising clinical trial experience are anti-CD40 ligand and rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC Pharmaceutical Corporation, San Diego, CA).
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PMID:Overview of idiopathic thrombocytopenic purpura: new approach to refractory patients. 1122 7

The availability of effective monoclonal antibodies (mAbs) has revolutionised the management of patients with B-cell malignancies. The most widely studied of these agents is rituximab (Rituxan, IDEC Pharmaceuticals, San Diego, CA), a chimeric anti-CD20 antibody. Using the standard 4-weekly administration schedule, rituximab induces responses in almost half of patients with relapsed follicular/low-grade (F/LG) non-Hodgkin's lymphoma (NHL) with complete remissions in 6%. Lower response rates (RRs) have been noted in chronic lymphocytic leukaemia (CLL) using the standard dose and schedule. The drug has been well tolerated in most patients with common adverse events including mild to moderate fevers and chills and rare occurrences of a serious syndrome related to cytokine release and rapid tumour clearance. This antibody is also active against aggressive NHL, mantle cell NHL, post-transplant lymphoproliferative disorder (PTLD), lymphoplasmacytic NHL and hairy cell leukaemia and is also being evaluated in autoimmune disorders. Combinations of rituximab with chemotherapy regimens such as CHOP (cyclophosphamide, adriamycin, vincristine, predinisone) may alter the therapeutic paradigm for these diseases. The future promise of this antibody is a foundation on which to develop new strategies to increase the cure of patients with lymphoid malignancies.
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PMID:Rituximab: clinical development and future directions. 1177 44

Advances in our understanding of normal B-cell differentiation have allowed for improved classification and therapy of B-cell malignancies. B-cell neoplastic diseases may be classified more accurately according to the differentiation stages of presumed normal B-cell counterparts. These advances have challenged the notion that chronic lymphocytic leukemia represents a malignancy of naive CD5 B cells. Analyses of immunoglobulin genes and gene expression patterns through microarray have defined at least two types of chronic lymphocytic leukemia that differ in their tendency toward disease progression. Nevertheless, these types still share more in common than they do with other lymphoid malignancies, and both may be derived from memory-type B cells. Advances in immune therapy are revolutionizing the approach to therapy. B-cell surface differentiation antigens constitute tissue-specific targets for passive immune therapy. Since the US Food and Drug Administration approval of rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA) for use in the treatment of follicular lymphoma, monoclonal antibody therapy is being considered for all types of B-cell malignancies. The ability to transform leukemia and lymphoma B cells into effective antigen-presenting cells through CD40 ligation allows for autologous immune recognition of neoplastic cells. Together, active and passive immune approaches have potential for effective treatment of patients with these diseases.
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PMID:Advances in classification and therapy of indolent B-cell malignancies. 1184 96

Historically, treatment of chronic lymphocytic leukemia (CLL) essentially had been palliative. During the past two decades, effective new therapies for the treatment of CLL have emerged. The advent of fludarabine, a purine analog with activity against chlorambucil-resistant CLL, showed promising results with high response rates in previously untreated patients. These improvements in response and delays in disease progression have not translated into a survival benefit, indicating that chlorambucil may be the preferred first-line therapy when treatment is indicated. Allogeneic hematopoietic stem cell transplantation, by combining the cytoreductive effects of conditioning with a potent graft-versus-tumor effect, is the only treatment modality with the prospect of cure for patients with CLL. However, conventional hematopoietic stem cell transplantation can be offered only to select patients with CLL because of older age and comorbid conditions. Novel methods of transplantation exploiting the graft-versus-leukemia effect while reducing the toxicity of the pretransplant conditioning are promising approaches that may enable more patients to benefit from this therapy. Monoclonal antibodies such as rituximab or alemtuzumab (Campath-1H; llex Pharmaceuticals, San Antonio, TX) are agents with activity in untreated and resistant CLL. Efforts are being focused on combining these monoclonal antibodies with chemotherapy and the development of rationally designed drugs.
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PMID:Chronic lymphocytic leukemia. 1205 68

High mortality rates per square mile associated with liver cancer, lung cancer, kidney cancer, and leukemia have been reported in San Antonio. Without taking into account the underlying at-risk population, cancer mortality rates per square mile alone may give the public a misleading picture. This study conducts a geographic cluster analysis of mortality of the four types of cancer mentioned above, considering both mortality cases and the at-risk population. The analysis uses statewide cancer mortality data over an 8-year period from 1990 through 1997. Results from the study indicate that only one statistically significant cluster of liver cancer mortality cases exists in Bexar County and its adjacent counties compared with the rest of Texas. No clusters of lung cancer, kidney cancer, or leukemia exist in San Antonio.
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PMID:Are deaths from liver cancer, kidney cancer, and leukemia clustered in San Antonio? 1239 37

The Cancer and Leukemia Group B (CALGB) Genitourinary Committee has developed a broad range of clinical trials across most stages of bladder cancer. Recurrence rates of superficial bladder cancer after transurethral resection range from 50-70%. Although adjuvant bacillus Calmette-Guerin reduces the risk of disease recurrence or progression, only 30% of patients have long-term disease-free survival. Because the development of novel secondline agents is needed, the CALGB is evaluating the utility of intravesicle gemcitabine as well as an oral proapoptotic agent (CP-461). In patients with locally advanced disease with an increased risk of disease recurrence after cystectomy, a randomized trial of conventional chemotherapy versus sequential dose-dense therapy is under development. The gemcitabine/cisplatin combination has become a commonly used regimen for the treatment of advanced transitional cell carcinoma (TCC). The CALGB is undertaking a Phase II study that incorporates a fixed dose rate gemcitabine infusion in this regimen, together with a selective epidermal growth factor receptor tyrosine kinase inhibitor, Iressa (Astra Zeneca, Wilmington, DE). In patients with renal insufficiency, a regimen of carboplatin, gemcitabine, and Iressa is planned. Novel agents, including arsenic trioxide and trastuzumab (Herceptin; Genentech, Inc., South San Francisco, CA), are being evaluated as secondline therapy in patients with advanced TCC who have disease progression after frontline therapy.
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PMID:Overview of bladder cancer trials in the Cancer and Leukemia Group B. 1267 1


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